Pre-B cell lines proliferating for several months on stromal cells in the presence of interleukin 7 (IL-7) were established from fetal liver of (NZB x NZW)F1 mice. They express the B lineage-specific markers PB76, B220, and VpreB, but do not express surface immunoglobulin (sIg). Upon removal of IL-7 from the culture, they differentiate to sIg+ B cells that can then be stimulated by lipopolysaccharide to become IgM-secreting cells. Transfer of these pre-B cell lines into SCID mice leads to hypergammaglobulinemia of IgM (600-900 micrograms/ml), IgG2a (1-3 mg/ml), and IgG3 (300-500 micrograms/ml) for the next 3-5 mo. The spleen appears populated with (NZB x NZW)F1-derived pre-B cells, few B cells, and many IgM and/or IgG-producing plasma cells. In contrast, SCID mice populated with pre-B cell lines of normal (C57BL/6 x DBA/2)F1 mouse fetal liver develop normal levels of serum IgM (approximately 100-300 micrograms/ml), almost no detectable levels of IgG, and no plasma cell hyperplasia. The (NZB x NZW)F1 pre-B cell-populated SCID mice contain elevated serum titers of IgG antinuclear autoantibodies, but no retroviral gp70-specific nor erythrocyte-specific autoantibodies. Up to 20% of the SCID mice develop proteinuria as a consequence of IgG deposits in the kidney glomeruli during a 7-mo period of observation. All signs of autoimmune disease seen in these mice are independent of the sex of the SCID host. This experimental system provides a distinction between the disease-determining (NZB x NZW)F1 genes, which are expressed in the B lymphocyte lineage and cause the development of the disease, from those expressed in other cell lineages which only modulate its progression.
Article|
November 01 1992
Development of autoimmune disease in SCID mice populated with long-term "in vitro" proliferating (NZB x NZW)F1 pre-B cells.
L Reininger,
L Reininger
Basel Institute for Immunology, Switzerland.
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T Radaszkiewicz,
T Radaszkiewicz
Basel Institute for Immunology, Switzerland.
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M Kosco,
M Kosco
Basel Institute for Immunology, Switzerland.
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F Melchers,
F Melchers
Basel Institute for Immunology, Switzerland.
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A G Rolink
A G Rolink
Basel Institute for Immunology, Switzerland.
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L Reininger
Basel Institute for Immunology, Switzerland.
T Radaszkiewicz
Basel Institute for Immunology, Switzerland.
M Kosco
Basel Institute for Immunology, Switzerland.
F Melchers
Basel Institute for Immunology, Switzerland.
A G Rolink
Basel Institute for Immunology, Switzerland.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1992) 176 (5): 1343–1353.
Citation
L Reininger, T Radaszkiewicz, M Kosco, F Melchers, A G Rolink; Development of autoimmune disease in SCID mice populated with long-term "in vitro" proliferating (NZB x NZW)F1 pre-B cells.. J Exp Med 1 November 1992; 176 (5): 1343–1353. doi: https://doi.org/10.1084/jem.176.5.1343
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